Characterization of <scp>AICAR</scp> transformylase/<scp>IMP</scp> cyclohydrolase (<scp>ATIC</scp>) from <i>Staphylococcus lugdunensis</i>

Verma, Preeti; Kar, Bibekananda; Varshney, Ritu; Roy, Partha; Sharma, Ashwani

doi:10.1111/febs.14303

Cited by 15 publications

(13 citation statements)

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“…The K m of the AF1811 protein product was estimated at 7.8 ± 1.8 μM with a k cat of 1.32 ± 0.14 s -1 under the 50°C assay conditions. As summarized in Table 2, AF1811 has a slightly weaker binding affinity than full-length PurH enzymes from human [11] and Staphylococcus lugdunensis [10]. AF1811 is also less catalytically active than these two previously-assayed PurH enzymes, but this difference may be at least partially attributable to the AF1811 kinetics experiment being conducted at 50°C, well below this organism’s optimal growth temperature of 76°C [17].…”

Section: Resultsmentioning

confidence: 99%

“…Studies on human PurH have shown that there is no channeling between the AICAR formyltransferase domain (PurH1) and the IMP cyclohydrolase domain (PurH2) [8]. Although they are nearly always fused in the non-archaea, the human PurH1 and PurH2 domains are functional when individually produced [9], as are those of Staphylococcus lugadensis [10]. Despite a pronounced trend towards production of full-length PurH in non-archaea, examination of the Archaea revealed predicted PurH2s without fusion to PurH1 in the Archaeoglobi [1].…”

Section: Introductionmentioning

confidence: 99%

“…Despite a pronounced trend towards production of full-length PurH in non-archaea, examination of the Archaea revealed predicted PurH2s without fusion to PurH1 in the Archaeoglobi [1]. The Archaeoglobus fulgidus locus AF1811 encodes a protein with only 25% amino acid identity to the characterized human protein [11], and only 29% identity to the characterized Staphylococcus lugadensis protein [10]. In this paper, we report the first characterization of the gene product of Archaeoglobus fulgidus AF1811, predicted to be an unfused PurH2 domain, which is also the first characterization of any sort of PurH from the domain Archaea.…”

Section: Introductionmentioning

confidence: 99%

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Experimental characterization of two archaeal inosine 5'-monophosphate cyclohydrolases

et al. 2019

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There is variability as to how archaea catalyze the final step of de novo purine biosynthesis to form inosine 5’-monophosphate (IMP) from 5-formamidoimidazole-4-carboxamide ribonucleotide (FAICAR). Although non-archaea almost uniformly use the bifunctional PurH protein, which has an N-terminal IMP cyclohydrolase (PurH2) fused to a C-terminal folate-dependent aminoimidazole-4-carboxamide ribonucleotide (AICAR) formyltransferase (PurH1) domain, a survey of the genomes of archaea reveals use of PurH2 (with or without fusion to PurH1), the “euryarchaeal signature protein” PurO, or an unidentified crenarchaeal IMP cyclohydrolase. In this report, we present the cloning and functional characterization of two representatives of the known IMP cyclohydrolase families. The locus TK0430 in Thermococcus kodakarensis encodes a PurO-type IMP cyclohydrolase with demonstrated activity despite its position in a cluster of apparently redundant biosynthetic genes, the first functional characterization of a PurO from a non-methanogen. Kinetic characterization reveals a Km for FAICAR of 1.56 ± 0.39 μM and a kcat of 0.48 ± 0.04 s-1. The locus AF1811 from Archaeoglobus fulgidus encodes a PurH2-type IMP cyclohydrolase. This Archaeoglobus fulgidus PurH2 has a Km of 7.8 ± 1.8 μM and kcat of 1.32 ± 0.14 s-1, representing the first characterization of an archaeal PurH2 and the first characterization of PurH2 that naturally occurs unfused to an AICAR formyltransferase domain. Each of these two characterized IMP cyclohydrolases converts FAICAR to IMP in vitro, and each cloned gene allows the growth on purine-deficient media of an E. coli purine auxotroph lacking the purH2 gene.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Experimental characterization of two archaeal inosine 5'-monophosphate cyclohydrolases

et al. 2019

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“…Cancer cells maintain a high level of de novo purine synthesis, in order to maintain rapid growth (9). 5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC, also known as AICAR) is an enzyme that can catalyse the last two reactions in the de novo purine biosynthetic pathway (10). Recently, it has been reported that ATIC is frequently upregulated and is important for cancer progression and development.…”

Section: Introductionmentioning

confidence: 99%

ATIC facilitates cell growth and migration by upregulating Myc expression in lung adenocarcinoma

Niu

Zeng

et al. 2022

Oncol Lett

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5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), a catalysing enzyme in the de novo purine biosynthetic pathway, has been previously reported to be upregulated and to participate in myeloma and hepatocellular carcinoma progression. In the present study, by using bioinformatics technology, a higher ATIC expression was identified in lung adenocarcinoma (LUAD) tissues than in normal tissues, and ATIC expression was found to be positively associated with Myc expression in LUAD tissues. In addition, the role of ATIC in modulating the growth and migration of LUAD cells was explored and the involvement of Myc was revealed. ATIC expression in 56 paired LUAD and tumour adjacent non-cancerous tissues was assessed using reverse transcription-quantitative PCR and western blot analysis. Pearson's correlation analysis was applied to evaluate the correlation between ATIC and Myc expression levels in LUAD tissues. A rescue experiment was performed to explore the role of ATIC/Myc in regulating the growth, migration and invasion of HCC827 and NCI-H1435 cells. It was demonstrated that ATIC was overexpressed in LUAD tissues, particularly in advanced-stage LUAD, and was predicted to be associated with an advanced TNM stage, a higher lymph node metastasis rate, poor tissue differentiation and a lower overall survival rate. ATIC overexpression promoted cell growth, migratory and invasive capacities, whereas this effect was abrogated by Myc knockdown in the HCC827 and NCI-H1435 cells. On the whole, the present study demonstrates that ATIC promotes LUAD cell growth and migration by increasing Myc expression.

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“…The role of 5‐aminoimidazole‐4‐carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) has not yet been well studied in the cancer area; ATIC encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. Its N‐terminal domain possesses a phosphoribosylaminoimidazolecarboxamide formyltransferase function, and the C‐terminal domain exhibits IMP cyclohydrolase activity, 11,12 which makes it possible to influence the carcinogenesis. An example is in hepatocellular carcinoma (HCC), as upregulation of ATIC has been reported in HCC tissue samples.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of ATIC in multiple myeloma tissues based on tissue microarray and gene microarrays

Chen

Dang

et al. 2020

Int J Lab Hematology

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Purpose Multiple myeloma (MM) is characterized by the malignant proliferation of plasma cells, which produce a monoclonal immunoglobulin protein. The role of 5‐aminoimidazole‐4‐carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) has not yet been well studied in the area of MM. Thus, in the current study, we sought to examine the expression levels, including mRNA and protein levels of ATIC in MM. Methods Multiple myeloma microarray and RNA‐seq data were screened from the SRA, GEO, ArrayExpress, and Oncomine databases. The mRNA level of ATIC was extracted from the high throughput data, and the prognostic value was studied. The protein level of ATIC was also detected by in‐house immunohistochemistry on a tissue microarray. Potential signaling pathways were enriched with ATIC‐related genes in MM. Results Both the mRNA and protein levels of ATIC were significantly upregulated in MM samples as compared to normal samples. Furthermore, the summarized Standardized Mean Difference was 1.66 with 674 cases of MM based on 10 independent studies including the in‐house tissue microarray. The overall hazard ratio of ATIC in MM was 1.7 with 1631 cases of MM based on five microarrays. In the KEGG pathway analysis, the ATIC‐related genes were mainly enriched in the pathway of complement and coagulation cascades. Conclusion We provided the first evidence supporting the upregulation of ATIC may play an essential part in the tumorigenesis and development of MM. The promoting cancer capacity may be related to the pathway of complement and coagulation cascades.

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Characterization of AICAR transformylase/IMP cyclohydrolase (ATIC) from Staphylococcus lugdunensis

Cited by 15 publications

References 45 publications

Experimental characterization of two archaeal inosine 5'-monophosphate cyclohydrolases

Experimental characterization of two archaeal inosine 5'-monophosphate cyclohydrolases

ATIC facilitates cell growth and migration by upregulating Myc expression in lung adenocarcinoma

Upregulation of ATIC in multiple myeloma tissues based on tissue microarray and gene microarrays

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